Studies Highlight Link Between Antipsychotics and Weight Gain

It’s one of the drawbacks to better mental health for anyone struggling with mental illness. Antipsychotics restore some balance to mental health but typically come with some degree of weight gain.

A 2021 research project, for example, found that antipsychotic drugs, scientists showed, not only block dopamine signaling in the brain but also in the pancreas, leading to uncontrolled production of blood glucose-regulating hormones and, eventually, obesity and diabetes.

The Journal of Clinical Psychiatry and The Primary Care Companion for CNS Disorders have published multiple papers over the last year that dig deep into the frustrating link between antipsychotics and metabolic functions. Here are summaries as well as links to these studies for further review.

Associations of Valproate Doses With Weight Gain in Adult Psychiatric Patients

Valproate (VPA) is a medication used to treat seizures, migraines, and bipolar disorder. Unfortunately, weight gain is a common side effect, with potential long-term consequences such as chronic obesity and metabolic disorders.

However, the association between VPA dosage and metabolic outcomes in psychiatric patients remains unclear. So researchers launched this study, which appeared in JCP in March, to assess this link in a cohort of Swiss psychiatric patients.

The researchers analyzed data from two longitudinal studies involving patients starting VPA treatment. The team examined a variety of factors, including dosage, treatment duration, and metabolic variables for a year.

Results revealed a positive association between VPA dose and weight gain, particularly for doses equal to or above 1,300 mg/day. Patients receiving higher doses experienced greater weight gain, especially after three months of treatment. Notably, men appeared to be more susceptible to weight gain than women.

However, the researchers failed to uncover any significant associations between VPA dose and changes in blood glucose, lipid levels, or blood pressure over a six-month treatment period.

Despite the study’s limitations, including the lack of lifestyle data and incomplete drug history, the authors report that the findings suggest the importance of closely monitoring patients on VPA for weight gain and considering prescribing the lowest effective doses to minimize metabolic consequences.

In conclusion, this study provides valuable insights into the association between VPA dosage and weight gain in psychiatric patients. It highlights the need for cautious prescribing practices and regular monitoring to mitigate adverse effects.

Weight Loss Medication Phentermine-Induced Hypomania in Bipolar Depression

Patients with bipolar disorder often experience weight gain, partly due to the chronic nature of the condition and medication side effects.

Phentermine, an FDA-approved appetite suppressant for short-term use in obesity, has been associated with triggering manic or hypomanic episodes, particularly in individuals with bipolar disorder. Despite its efficacy in weight loss, phentermine’s potential for abuse and neuropsychiatric side effects, such as insomnia, mood swings, and agitation, warrants caution, especially when used in conjunction with antidepressants or other medications affecting neurotransmitter balance.

This case study, which PCP published in February, presented a 40-year-old woman with bipolar II disorder and morbid obesity who experienced a hypomanic episode after her doctor prescribed phentermine alongside mood stabilizers and antidepressants.

This case study illustrated the need for careful consideration when prescribing weight loss medications to patients with bipolar disorder. They could exacerbate mood symptoms and lead to treatment non-compliance or even functional impairment.

Furthermore, the combination of phentermine with other medications, particularly antidepressants, poses additional risks of serotonin syndrome or hypertensive crisis. While phentermine remains a widely prescribed anti-obesity medication, clinicians should closely monitor patients, especially those with bipolar disorder, for signs of mood destabilization or hypomania.

The scientific community still lacks long-term safety data on the use of phentermine in this population, highlighting the importance of ongoing research to better understand its risks and benefits in individuals with comorbid mental health conditions.

Comparative Effects of Antipsychotics on Weight Gain and Metabolic Function in Schizophrenia Patients

Schizophrenia is a severe mental illness linked to social isolation, occupational disability, and poor physical health, including a reduced life expectancy mainly due to cardiovascular disease. Antipsychotic medications remain the primary treatment but persistent evidence insists that it includes adverse effects such as weight gain and metabolic disturbances, exacerbating cardiovascular risks. Patients with schizophrenia receive lower-quality cardiovascular care, posing challenges for clinicians in balancing medication benefits and adverse effects.

To personalize treatment, medical professionals must understand the dose-dependent effects of antipsychotics on weight gain and metabolic disturbance.

Researchers conducted a systematic review and dose-response meta-analysis of 52 randomized controlled trials (RCTs) involving 22,588 participants and 11 antipsychotics. Each antipsychotic exhibited a distinct dose-response association with weight gain and metabolic variables. Some antipsychotics, like brexpiprazole, cariprazine, haloperidol, lurasidone, and quetiapine extended-release, showed quasi-parabolic curves, indicating less weight gain at higher doses.

Others, such as asenapine, iloperidone, paliperidone long-acting injectable (LAI), quetiapine immediate-release, and oral risperidone, presented plateau-shaped curves, suggesting minimal additional weight gain at higher doses.

Conversely, aripiprazole, oral and LAI olanzapine, risperidone LAI, and oral paliperidone demonstrated ascending curves, indicating continued weight gain with higher doses. Olanzapine showed the most pronounced weight gain and significant metabolic disturbances, raising concerns about its first-line use.

Notably, lower doses might provide a better balance between efficacy and metabolic side effects for some antipsychotics.

Limitations include a limited number of studies and varying study durations. Future research should encompass a broader range of doses and long-term metabolic parameter assessments. These findings provide valuable insights for clinicians in tailoring antipsychotic treatment to minimize adverse effects while optimizing symptom control in schizophrenia patients.

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